title: Renal impairment is frequent in chronic hepatitis C patients under triple therapy with telaprevir or boceprevir.
abstract: In clinical trials with telaprevir (TLV) and boceprevir (BOC) renal impairment was not reported as a relevant adverse event. The PAN study is a noninterventional study enrolling patients treated with peginterferon alfa-2a/ribavirin (PEG/RBV) with or without TVL or BOC. Here we restrict the analysis to hepatitis C virus genotype 1 patients having completed 12 (n = 895) or 24 weeks (n = 591) of treatment. For estimation of glomerular filtration rate (eGFR) the Chronic Kidney Disease Epidemiology Collaboration (CKD-EPI) formula was chosen. Patients on TLV 38/575 (6.6%) and BOC 10/211 (4.7%) more frequently experienced a decrease in eGFR to <60 mL/min compared to patients on PEG/RBV 1/109 (0.9%) (P < 0.05). Risk factors associated with eGFR <60 mL/min in multiple logistic regression analysis were age (P < 0.001), arterial hypertension (P < 0.05), higher serum creatinine at baseline (P < 0.001), and being on triple therapy with TLV or BOC (P < 0.01). Patients with an eGFR of <60 mL/min had a lower absolute mean hemoglobin at week 12 compared to patients with an eGFR >60 mL/min (9.7 g/dL ± 1.4 g/dL versus 11.0 g/dL ± 1.7 g/dL) (P < 0.001). Most patients on TLV with a decrease of eGFR <60 mL/min showed a marked improvement in renal function after discontinuation of TLV.
  
  
  CONCLUSIONS
  Renal impairment has not been reported as a safety signal in clinical trials with TVL or BOC. However, in this large cohort including patients with risk factors for renal impairment a marked decline in renal function was observed in about 5% of patients on triple therapy. In addition to being a safety concern, substantial ribavirin dose reductions have to be considered in these patients, as anemia was more pronounced in patients with impaired renal function.
authors.affiliation: Center for HIV and Hepatogastroenterology, Duesseldorf, Germany.
authors.forename: Stefan
authors.initials: S
authors.lastname: Mauss
authors.forename: Dietrich
authors.initials: D
authors.lastname: Hueppe
authors.forename: Ulrich
authors.initials: U
authors.lastname: Alshuth
mesh_terms: D000328:Adult; D000998:Antiviral Agents / Q000627:therapeutic use; D004359:Drug Therapy, Combination; D005260:Female; D005919:Glomerular Filtration Rate; D019698:Hepatitis C, Chronic / Q000188:drug therapy*; D006801:Humans; D007372:Interferons / Q000627:therapeutic use; D008297:Male; D008875:Middle Aged; D009842:Oligopeptides / Q000009:adverse effects*; D011392:Proline / Q000009:adverse effects / Q000031:analogs & derivatives*; D051437:Renal Insufficiency / Q000139:chemically induced*
chemical_list: D000998:Antiviral Agents; D009842:Oligopeptides; C486464:telaprevir; C512204:N-(3-amino-1-(cyclobutylmethyl)-2,3-dioxopropyl)-3-(2-((((1,1-dimethylethyl)amino)carbonyl)amino)-3,3-dimethyl-1-oxobutyl)-6,6-dimethyl-3-azabicyclo(3.1.0)hexan-2-carboxamide; D007372:Interferons; D011392:Proline